Adolescent pregnancy is one of the most serious public health problems in the United States. The costs associated with its adverse medical and socioeconomic consequences total 6 billion dollars annually. Americans incur these costs, at least partially, because of an incomplete understanding of the reasons that teens are twice as likely as adults to deliver prematurely. Efforts to prevent this important cause of infant morbidity and mortality have been unsuccessful, largely because of insufficient knowledge of the pathophysiologic mechanisms that predispose teens to pre-term delivery. A mid-career investigator award would expand the time the candidate has for patient-oriented research on the causes of the disproportionate number of pre-term teen births, enable her to involve more beginning researchers in her studies, and allow her to provide the mentoring they need to become independent clinical investigators. The overarching hypothesis the candidate will test is that the psychologic stress associated with early childbearing exacerbates teens' physiologic vulnerability to pre-term delivery by impeding placentation. In Specific Aim 1, data she has compiled are used to: 1) develop new composite indices of adolescent maternal stress; 2) model the interaction among these stresses, the physical changes of puberty, and traditional risk factors for pre-term delivery; and 3) create the infrastructure for a national teen-pregnancy databank capable of standardizing and pooling data from multiple sites. In Specific Aim 2, novel immunocytochemical analyses are used to study cytotrophoblastic stem cell differentiation with the goals of establishing a mechanistic link between young maternal age, abnormal placentation and, pre-term delivery and generating testable new hypotheses about therapeusis. The candidate is a clinician-scholar in her 12th post-fellowship year. She has demonstrated novel clinical pathophysiologic correlations among specific aspects of female reproductive development and pre-term delivery and presented her findings at national meetings and in peer-reviewed publications. As a mentor she has increased the pool of new clinical investigators conducting independent research in adolescent medicine. This award will contribute to her career goal of combining hypothesis driven clinical research, mentoring new beginning investigators in adolescent medicine, and innovative patient care.